U.S. patent number 6,471,069 [Application Number 09/727,162] was granted by the patent office on 2002-10-29 for device for separating components of a fluid sample.
This patent grant is currently assigned to Becton Dickinson and Company. Invention is credited to Paul C. DiCesare, Fu-Chung Lin, Jeffrey Radziunas.
United States Patent |
6,471,069 |
Lin , et al. |
October 29, 2002 |
Device for separating components of a fluid sample
Abstract
A device and method for separating heavier and lighter fractions
of a fluid sample. The device includes a flexible collapsible inner
container disposed within a substantially rigid outer container. A
closure seals the open top end of the outer container. A filter
assembly is sealingly mounted to the open top end of the inner
container. The filter assembly includes a filter that permits
lighter fractions to pass therethrough, while substantially
blocking the heavier fractions. The filter assembly further
includes a filter support having a slit valve registered with the
filter. The slit valve opens in response to fluid pressure created
by the lighter fractions for permitting the lighter fractions to
flow therethrough. A fluid sample is delivered to the inner
container and the device is subjected to centrifugation whereby the
centrifugal load causes the filter assembly to move toward the
bottom end of the outer container and thereby enable the lighter
fraction of the fluid sample to flow through the slit valve and
into the space between the inner and outer containers. The slit
valve closes upon termination of the centrifugal load such that
separation between the heavier and lighter fractions of the fluid
sample are maintained.
Inventors: |
Lin; Fu-Chung (Wayne, NJ),
DiCesare; Paul C. (Norwalk, CT), Radziunas; Jeffrey
(Wallingford, CT) |
Assignee: |
Becton Dickinson and Company
(Franklin Lakes, NJ)
|
Family
ID: |
22613063 |
Appl.
No.: |
09/727,162 |
Filed: |
November 30, 2000 |
Current U.S.
Class: |
210/359;
210/360.1; 210/515; 210/516; 210/518; 422/561; 422/72; 436/177;
494/16 |
Current CPC
Class: |
B01L
3/5021 (20130101); B01L 3/50215 (20130101); B01L
3/50825 (20130101); B01L 2400/0605 (20130101); B01L
2400/0638 (20130101); Y10T 436/25375 (20150115) |
Current International
Class: |
B01L
3/14 (20060101); B01D 021/26 (); C01N 033/49 ();
B01L 003/14 () |
Field of
Search: |
;210/359,360.1,515,516,518 ;422/72,101,102 ;494/16 ;436/177 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0 017 127 |
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Mar 1980 |
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EP |
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0 627 261 |
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Jun 1994 |
|
EP |
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0 638 804 |
|
Aug 1994 |
|
EP |
|
6-222055 |
|
Aug 1994 |
|
JP |
|
Primary Examiner: Reifsnyder; David A.
Attorney, Agent or Firm: Thomas, Esq.; Nanette S.
Parent Case Text
This application claims the benefit of U.S. provisional application
Ser. No. 60/168,819 filed Dec. 3, 1999, the disclosure of which is
hereby incorporated by reference.
Claims
What is claimed is:
1. An assembly comprising: an outer container having a bottom end,
an open top end and a substantially rigid sidewall enclosure
extending therebetween; an inner container disposed within said
outer container, said inner container having a bottom end in
proximity to said bottom end of said outer container, an open top
end and a flexible collapsible sidewall enclosure extending
therebetween; a closure sealingly engaged with said open top end of
said outer container for defining a sealed space between said inner
and outer containers; and a filter assembly movably disposed within
said outer container and sealingly engaged with said open top of
said inner container, said filter assembly comprising a filter that
permits less dense phase of a liquid sample to flow therethrough
and prevents more dense phase of the liquid sample from flowing
therethrough.
2. The assembly of claim 1, wherein the filter assembly further
includes a filter support surrounding portions of said filter
externally of said inner container, said filter support including
at least one valve that is openable in response to fluid pressure
thereon for permitting a flow of said less dense phase liquid
through said filter assembly and into a space between said inner
and outer containers.
3. The assembly of claim 2, wherein the valve is a slit valve.
4. The assembly of claim 3, wherein said filter is substantially
tubular and has an inner circumferential surface, an outer
circumferential surface, a bottom end and a top end, said bottom
end of said filter and said inner circumferential surface thereof
being in communication with interior portions of said inner
container, said filter support including a cylindrical outer wall
surrounding and engaging said outer circumferential surface of said
filter, said filter support further having a top wall extending
across one end of said cylindrical outer wall of said filter
support, said at least one slit valve being substantially
registered with said top end of said filter.
5. The assembly of claim 4, wherein said at least one slit valve
comprises a plurality of arcuate slit valves.
6. The assembly of claim 4, wherein said filter support further
comprises an inner cylindrical wall depending from said top wall of
said filter support and engaging a portion of said inner
circumferential surface of said filter.
7. The assembly of claim 4, wherein portions of said inner
container adjacent said open top thereof are sealingly engaged
between said filter and said filter support.
8. The assembly of claim 7, wherein said filter support further
comprises an annular bottom wall extending inwardly from portions
of said cylindrical outer wall of said filter support remote from
said top wall, said bottom wall of said filter support engaging a
portion of said bottom end of said filter for retaining said filter
in said filter support.
9. The assembly of claim 8, wherein portions of said inner
container adjacent said open top thereof are sealingly engaged
between said bottom end of said filter and said bottom wall of said
filter support.
10. The assembly of claim 4, wherein said outer container is
unitarily formed and has a closed bottom, and wherein said inner
container is unitarily formed and has a closed bottom.
11. The assembly of claim 4, wherein said closure and said top wall
of said filter support each include a central portion that is
pierceable by a needle for depositing a sample of blood in said
inner container, said closure being formed from a resealable
elastomeric material.
12. The assembly of claim 3, wherein said filter comprises
substantially circular top and bottom ends and a cylindrical outer
surface extending therebetween, said filter being substantially
continuous between said top and bottom ends and inwardly of said
outer circumferential surface, and wherein said filter support
comprises a cylindrical outer wall surrounding and engaging said
outer cylindrical surface of said filter and a circular top wall
substantially abutting said circular top surface of said filter,
said at least one slit valve being formed in said top wall of said
filter support.
13. The assembly of claim 12, wherein said filter support further
comprises an annular bottom wall extending inwardly from portions
of said cylindrical outer wall of said filter support remote from
said top wall, said bottom wall of said filter support engaging
portions of said bottom surface of said filter adjacent said outer
cylindrical surface thereof.
14. The assembly of claim 12, wherein portions of said inner
container adjacent said open top thereof are sealingly engaged
between said filter support and said filter.
15. The assembly of claim 12, wherein said inner and outer
containers each have open bottom ends, a needle pierceable closure
being sealingly engaged with portions of said inner and outer
containers adjacent said open bottom ends thereof, said bottom
closure including a resealable septum for permitting passage of a
needle cannula therethrough for depositing a sample of blood within
said inner container.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a device and method for separating
heavier and lighter fractions of a fluid sample. More particularly,
this invention relates to a device and method for collecting and
transporting fluid samples whereby the device and fluid sample are
subjected to centrifugation in order to cause separation of the
heavier fraction from the lighter fraction of the fluid sample.
2. Description of Related Art
Diagnostic tests may require separation of a patient's whole blood
sample into components, such as serum or plasma, the lighter phase
component, and red blood cells, the heavier phase component.
Samples of whole blood are typically collected by venipuncture
through a cannula or needle attached to a syringe or an evacuated
collection tube. Separation of the blood into serum or plasma and
red blood cells is then accomplished by rotation of the syringe or
tube in a centrifuge. Such arrangements use a barrier for moving
into an area adjacent the two phases of the sample being separated
to maintain the components separated for subsequent examination of
the individual components.
A variety of devices have been used in collection devices to divide
the area between the heavier and lighter phases of a fluid
sample.
The most widely used device includes thixotropic gel materials such
as polyester gels in a tube. The present polyester gel serum
separation tubes require special manufacturing equipment to prepare
the gel and to fill the tubes. Moreover, the shelf-life of the
product is limited in that overtime globules may be released from
the gel mass. These globules have a specific gravity that is less
than the separated serum and may float in the serum and may clog
the measuring instruments, such as the instrument probes used
during the clinical examination of the sample collected in the
tube. Such clogging can lead to considerable downtime for the
instrument to remove the clog.
No commercially available gel is completely chemically inert to all
analytes. If certain drugs are present in the blood sample when it
is taken, there can be an adverse chemical reaction with the gel
interface.
Therefore, a need exists for a separator device that (I) is easily
used to separate a blood sample; (ii) is independent of temperature
during storage and shipping; (iii) is stable to radiation
sterilization; (iv) employs the benefits of a thixotropic gel
barrier yet avoids the many disadvantages of placing a gel in
contact with the separated blood components; (v) minimizes cross
contamination of the heavier and lighter phases of the sample
during centrifugation; (vi) minimizes adhesion of the lower and
higher density materials against the separator device; (vii) is
able to move into position to form a barrier in less time than
conventional methods and devices; (viii) is able to provide a
clearer specimen with less cell contamination methods and devices;
and (ix) can be used with standard sampling equipment.
SUMMARY OF THE INVENTION
The present invention is a method and assembly for separating a
fluid sample into a higher specific gravity phase and a lower
specific gravity phase. Desirably, the assembly of the present
invention includes a rigid outer container, a flexible inner
container and a filter assembly for providing communication between
the inner and outer containers.
The outer container may be a tube having opposed longitudinal ends
and a substantially cylindrical sidewall extending therebetween.
Both ends of the tube are substantially closed or closeable. For
example, one end of the tube may have a permanent closure extending
unitarily from the cylindrical sidewall of the tube. The opposed
end of the tube may be substantially open, but may receive a needle
pierceable resealable closure. Alternatively, both ends of the tube
may be open, and both open ends of the tube may be sealed by
elastomeric closures. At least one of the closures of the tube may
include a needle pierceable resealable septum.
The inner container may be a flexible collapsible tubular bag
formed from a transparent plastic material. The inner container is
disposed within the outer container, and in a non-collapsed state
may extend substantially between the opposed ends of the outer
container. However, the inner container, such as the tubular
plastic bag, is selectively collapsible toward one end of the outer
container.
The filter assembly comprises a filter that is operative to permit
blood serum to pass therethrough. However, the filter will
substantially prevent the more dense red blood cells from passing
therethrough. The filter assembly further includes a filter support
in which the filter is securely retained. The filter support may
comprise a cylindrical sidewall having opposed longitudinal ends.
An end wall may extend across one longitudinal end of the
cylindrical sidewall of the filter support. The end wall includes
at least one slit valve formed therein. The slit valve is disposed
at a location on the end wall that will substantially register with
the filter. For example, the filter may define a substantially
thick-walled tube retained by the support of the filter assembly.
In this embodiment, the slit valve may define arc sections disposed
on portions of the end wall that will register with one end of the
tubular filter. In other embodiments, the filter may effectively
define a continuous cylindrical plug that is securely engaged
within the filter support. In this embodiment, the slit valve can
take other configurations, such as a short diametrically aligned
slit in the circular end wall.
In all embodiments, the filter assembly is dimensioned to be
slidably moveable within the outer container. Additionally, the
filter assembly and the flexible inner container define a secure
fluid tight connection therebetween. For example, a tubular plastic
bag defining the flexible inner container may have portions
adjacent the open end disposed between the filter and inner surface
areas of the filter support.
In use, a fluid sample enters the assembly by needle. The needle
penetrates through the resealable closure and is urged into
communication with the interior of the flexible inner container.
The sample is then directed into the flexible inner container. The
assembly is then placed in a centrifuge such that the filter
assembly is at a radially inner position relative to the fluid
sample within the flexible inner container. The centrifuge then is
operated to place a centrifugal load on the assembly. The
centrifugal load causes the more dense phase liquid to move
outwardly relative to the axis of rotation of the centrifuge, and
simultaneously causes the less dense phase liquid to move into
locations closer to the axis of rotation of the centrifuge. The
centrifugal load also causes the filter assembly to move away from
the axis of rotation of the centrifuge. As a result, the less dense
phase liquid is urged into the filter. The centrifugal load also
causes the less dense phase liquid to open the slit valve
sufficiently for the serum to flow out of the flexible inner
container and into the space between the inner and outer
containers. The outflow of the less dense phase liquid from the
inner container causes the walls of the flexible inner container to
collapse gradually, thereby decreasing the volume of the inner
container. Simultaneously, there is a corresponding increase in the
volume between the inner and outer containers as the less dense
phase liquid flows through the filter assembly. After sufficient
centrifugation, substantially all of the less dense phase liquid
will have passed through the filter assembly. However, the filter
prevents a flow of the more dense phase liquid therethrough. As a
result, the more dense phase liquid is retained within the inner
container, while the less dense phase liquid is retained in the
space between the inner and outer containers. Additionally, upon
termination of the centrifugal load, the less dense phase liquid
disposed in the space between the inner and outer containers will
not be subjected to any forces that would cause the less dense
phase liquid to migrate back across the filter assembly and into
the inner container. As a result, the two phases of the fluid
sample may be removed separately from their respective containers
and analyzed in a laboratory.
The assembly of the present invention is advantageous over existing
separation products that use gel. In particular the assembly of the
present invention will not interfere with analytes as compared to
gels that may interfere with analytes. Another attribute of the
present invention is that the assembly of the present invention
will not interfere with therapeutic drug monitoring analytes.
Another notable advantage of the present invention is that fluid
specimens are not subjected to low density gel residuals that are
at times available in products that use gel.
A further attribute of the present invention is that there is no
interference with instrument probes.
Another attribute of the present invention is that samples for
blood banking tests are more acceptable than when a gel separator
is used.
Additionally, the assembly of the present invention does not
require any additional steps or treatment by a medical
practitioner, whereby a blood or fluid sample is drawn in the
standard fashion, using standard sampling equipment.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is perspective view of the assembly of the present
invention.
FIG. 2 is a cross-sectional view of the assembly of FIG. 1 taken
along line 2--2 thereof and showing a needle depositing a sample of
fluid into the assembly.
FIG. 3 is a cross-sectional view of the assembly of FIG. 1 taken
along line 2--2 thereof, showing the assembly at an intermediate
stage of a centrifugation process.
FIG. 4 is a cross-sectional view of the assembly of FIG. 1 taken
along line 2--2 thereof, showing the assembly after completion of
centrifugation.
FIG. 5 is a perspective view of the flexible inner container and
the filter assembly of the assembly.
FIG. 6 is a cross-sectional view of the container and filter
assembly of FIG. 5 taken along line 6--6 thereof.
FIG. 7 is a cross-sectional view of the container and filter
assembly of FIG. 5 taken along 6--6 thereof, but showing an
alternate container assembly.
FIG. 8 is a cross-sectional view of the container and filter
assembly of FIG. 5 taken along 6--6 thereof, but showing an
alternate container assembly.
DETAILED DESCRIPTION
The present invention is illustrated in FIGS. 1-4 wherein assembly
10 includes an outer container 12, an inner container 14, a closure
16 and a filter assembly 18.
Outer container 12 is a rigid clear plastic or glass tube having an
open top 20, a closed bottom 22 and a cylindrical sidewall 24
extending between top 20 and bottom 22. Cylindrical sidewall 24
defines an inside diameter "a" as shown in FIG. 1.
Inner container 14 is formed from a flexible and collapsible clear
plastic material that is substantially impervious to fluid. Inner
container 14 has an open top end 26, a closed bottom end 28 and a
flexible collapsible sidewall 30 extending therebetween.
Closure 16 is formed from an elastomeric material and includes an
outer skirt 32 dimensioned for sealed telescoped engagement over
portions of cylindrical sidewall 24 of outer container 12 adjacent
open top 20 thereof. Additionally, closure 16 includes a plug
portion 34 dimensioned for sealed engagement within open top 20 of
outer container 12. The center region 36 of closure 16 is recessed
and defines a resealable septum through which a needle cannula 38
can be inserted. Upon removal of needle cannula 38, septum portion
36 will reseal itself.
Filter assembly 18 includes a filter 40 and a filter support 42.
Filter 40 is formed from a material that will permit the less dense
phase liquid to pass therethrough, while substantially preventing
the more dense phase from passing therethrough. Filters with these
performance specifications are commercially available and are
marketed, for example, by Becton Dickinson as an Auto
ISO-filter.
As shown in FIG. 6, filter 40 is a substantially thick-walled
tubular shape and includes an inner circumferential surface 44
defining an inside diameter b and an outer circumferential surface
46 defining an outside diameter c. Filter 40 further includes a top
end 48 and an opposed bottom end 50.
Filter support 42 is unitarily molded from a thermoplastic material
and includes an outer cylindrical sidewall 52 having an inside
diameter which is substantially equal to outside diameter c defined
by outer circumferential surface 46 of filter 40. Additionally,
outer cylindrical sidewall 52 defines an outside diameter which is
slightly less than inside diameter "a" defined by cylindrical
sidewall 24 of outer container 12. Relative dimensions of the outer
cylindrical sidewall 52 of filter support 42 and cylindrical
sidewall 24 of outer container 12 enable filter assembly 18 to move
slidably within outer container 12.
Filter support 42 further includes a generally circular top wall 54
extending substantially continuously across an end of cylindrical
sidewall 52 of filter support 42. Top wall 54 is characterized by a
pair of slit valves 56 extending arcuately at a location on top
wall 54 that registers with top end 48 of filter 40. Slit valves 56
remain substantially closed in an unbiased condition of top wall
54. However, in response to fluid forces exerted on top wall 54,
the thermoplastic material of top wall 54 adjacent slit valves 56
will deform sufficiently to permit fluid flow therethrough. Top
wall 54 is further characterized by a short inner cylindrical wall
58 extending downwardly therefrom and concentrically within outer
cylindrical wall 52. Inner cylindrical wall 58 defines an outside
diameter approximately equal to inside diameter b of inner
circumferential surface 44 of filter 40. With this construction,
filter 40 is effectively trapped between outer cylindrical wall 52
and inner cylindrical wall 58.
Filter support 42 further includes an annular bottom lip 60
extending inwardly from the end of outer cylindrical wall 52
opposite circular top wall 54. Lip 60 functions to retain filter 40
between lip 60 and top wall 54. Lip 60 may initially define a
cylindrical extension of outer circumferential wall 52, and
subsequently may be formed inwardly as explained herein.
Filter assembly 18 is assembled by slidably inserting tubular
filter 40 into the end of filter support 42 opposite top wall 54.
Portions of inner container 14 adjacent open top end 26 are
positioned adjacent portions of bottom end 50 of filter 40 adjacent
outer circumferential surface 46 of filter 40. The end of outer
cylindrical wall 52 of filter support 42 opposite top wall 54
thereof then is deformed inwardly to define lip 60. As a result,
filter 40 is securely retained in filter support 42 and inner
container 14 is securely engaged with filter assembly 18.
Assembly proceeds by sliding inner container 14 and filter assembly
18 into open top 20 of outer container 12. Container assembly 10
then is enclosed by sealingly mounting closure 16 onto open top 20
of outer container 12.
As shown in FIG. 2, a liquid sample is delivered into inner
container 14 by needle 38 that penetrates through resealable septum
portion 36 of stopper 16 and through portions of top wall 54 of
filter support 42. For purposes of illustration only, the liquid
sample is blood. The sample of blood then is deposited into the
inner container 14, as shown in FIG. 2, and is isolated from the
space between inner container 14 and outer container 12. Upon
removal of needle 38, septum portion 36 of closure 16 reseals
itself.
Assembly 10 next is placed in a centrifuge such that top end 20 of
outer container 12 is closer than the bottom end 22 to the axis of
rotation of the centrifuge. The centrifuge than is operated to
create centrifugal loading on blood sample 62. As shown in FIG. 3,
the centrifugal loading urges the filter assembly in the direction
indicated by arrow "A" toward bottom end 22 of outer container 12
and simultaneously generates a separation of the respective phases
of the blood sample 62 in accordance with their densities. More
specifically, red blood cells of blood sample 62 move away from the
rotational axis of the centrifuge and toward closed bottom end 28
of inner container 14. Simultaneously less dense serum moves toward
the rotational axis of the centrifuge and away from closed bottom
end 28 of inner container 14. The centrifugal loading that causes
this separation of the red blood cells 64 and serum 66 and that
causes the movement of filter assembly 18 within outer container 12
urges serum 66 through filter 40 also creates biasing forces on
portions of top wall 54 in proximity to slit valves 56. This
loading deflects top wall 54 at slit valves 56 into an open
condition that permits the flow of serum through slit valves 56 and
into the space between inner and outer containers 14 and 12
respectively. After sufficient centrifugation, only red blood cells
64 will remain within inner container, and substantially all of
serum 66 that had been in the initial blood sample will lie between
inner and outer containers 14 and 12 respectively as shown in FIG.
4. The centrifuge then is stopped, and top wall 54 resilient
returns to an unbiased condition in which slit valves 56 close.
Closure 16 then can be separated from open top 20 of outer
container 12 to enable serum 66 to be separated and to subsequently
enable access to red blood cells of the blood sample that are
isolated within inner container 14.
An alternate assembly 70 in accordance with the present invention
is shown in FIGS. 7 and 8. Assembly 70 includes a substantially
rigid clear plastic or glass outer container 72, a flexible
collapsible inner container 74, a closure 76 and a filter assembly
78.
Outer container 72 concludes an open top end 80, an open bottom end
82 and a rigid cylindrical sidewall 84 extending therebetween.
Sidewall 84 may define an inside diameter substantially the same as
the inside diameter of the sidewall 24 of the first embodiment.
Inner container 74 includes an open top end 86, an open bottom end
88 and a flexible sidewall extending therebetween.
Closure 76 is substantially identical to closure 16 described and
illustrated above. Additionally, filter assembly 78 is structurally
and functionally very similar to filter assembly 18 described and
illustrated above. More particularly, filter assembly 78 includes a
filter 90 and a filter support 92. Filter 90 is a substantially
solid cylindrical plug, as compared to the tubular filter of the
previous embodiment. Filter support 92 includes a cylindrical outer
sidewall 94 that surrounds filter 90 and a circular top wall 96
that extends across the continuous circular top end of filter 90.
Top wall 96 does not include a downwardly depending short
cylindrical inner wall comparable to the cylindrical inner wall of
the first embodiment. Thus, the circular top end of filter 90 can
abut circular top wall 96 of filter support 92. Top wall 96
includes at least one slit valve 98 that is comparable to the slit
valves 56 described and illustrated with respect to the first
embodiment. However, in view of the continuous solid cylindrical
configuration of filter 90, slit valves 98 may be disposed at any
convenient locations on top wall 96 of filter support 92. Open top
end 86 of inner container 74 is securely engaged with filter 90 and
filter support 92 substantially as described above.
Assembly 70 further includes a bottom closure 100 that is securely
engaged within the open bottom end 82 of outer container 72 and the
open bottom end 82 of the inner container 74. More particularly,
bottom closure 100 is dimensioned to sealingly hold inner and outer
container 74 and 72 respectively with one another at their open
bottom ends. Bottom closure 100 includes a resealable septum 102
which is structurally and functionally similar to the resealable
septum 36 of the top closure 16 described and illustrated
above.
Assembly 70 is used by initially depositing a sample of blood into
inner container 72 by passing a needle cannula 38 through septum
102 of bottom closure 100 and placing the blood sample in inner
container 74. The assembly then is centrifuged substantially as
described above. The centrifugation will cause filter assembly 78
to slidably move within outer container 72 and away from top
closure 76. Simultaneously, the centrifugation will cause red blood
cells of the collected blood sample to move toward bottom closure
100, while serum will be urged toward top closure 76. These
centrifugal loads will cause serum to pass through filter 90 and
the fluid pressure of the serum will open slit valves 98 such that
the serum of the blood sample will move into the space between
inner and outer containers 74 and 72 respectively. After the
respective phases of the blood sample have been completely
separated, the centrifuge is stopped. The removal of the
centrifugal load causes slit valves 98 to close, thereby
maintaining separation between the serum and the red blood cells.
Top closure 76 then is removed to access and remove the serum. The
red blood cells within the inner container then may be accessed for
subsequent analysis.
* * * * *